The objective of the proposed project is to elucidate the mechanisms by which glucocorticoids exert their permissive action on glucagon and catecholamine control of hepatic carbohydrate metabolism. Present findings indicate that adrenalectomy resulted in (1) a decrease in alpha-adrenergic and an increase in beta-adrenergic activities in the liver, (2) reduction in glucagon activation of glycogen phosphorylase due to impairment in the control of phosphorylase b kinase and possibly of phosphoprotein phosphate(s), and (3) a lack of glucagon action on pyruvate utilization and at the level of phosphofructokinase-fructosebisphosphatase correlating with a reduction in stimulation of gluconeogenesis. It is planned to study in detail the effects of adrenalectomy on hepatic alpha-receptor-ligand binding as well as on alpha-adrenergic control of subcellular calcium metabolism. The physiological significance of the reciprocal change in alpha- and beta-adrenergic actions will also be explored. The role of phosphorylase b kinase and phosphoprotein phosphatase in the steroid permissive effect on glucagon action will be studied in detail with special emphasis on possible effects of adrenalectomy on subcellular distribution of phosphatase(s) and their regulation by protein inhibitor(s). The effects of adrenalectomy on glucagon action on phosphofructokinase and mitochondrial pyruvate metabolism will be examined in the context of the lack of glucagon stimulation of gluconeogenesis.